Organo-mercapto-methyleneamides of o, o-dialkyl-thio(or dithio)-phosphorylacetic acids having pesticidal activity



The present invention relates to the preparation and the use of organo-mercapto-methylenamides of 0,0-di- 'alkyl-thioand dithiophosphorylacetic acids corresponding to the general formula:

where R- is preferably a normal or branched saturated or unsaturated alkyl or alkenyl or acycloaliphatic or aryl radical, substituted and unsubstituted; R is a lower alkyl radical, i.e. having. up to nine carbon atoms; and X is oxygen or sulfur.

The products of the present invent-ion are low melting point crystalline substances or liquids which are soluble in most organic solvents, and are generally waterinsoluble. The products have a wide range or spectrum of pesticide activity, and are usefully applied alone,- or in admixture with the common pesticides, such as insecticides or fungicides, and also in admixture with fertilizers.

They are prepared by reaction of mercaptans and N-methylol-amides of 0,0-dialky1-thioor dithiophosphoryl-acetic acids according tothe following. scheme:

R, R and X being defined as above.

Said reaction is carried out in the presence of an acid condensation agent, such as, for example, H 50 HCl', ZnCl CaCI etc., and with partial .or complete solution or suspension of both reactants in a. liquid solvent or dispersing agent. The liquid is preferably inert to one. or both reactants. The reaction is carried out at temperatures generally between 20 C. and 1-00 (3., ,at ordinary or atmospheric pressure, or under slight autogenetic pressure, particularly when operating with mercaptans of low boiling point. Ketones, esters, ethers, hydrocarbons, and mixtures thereof can be used as said liquid. The reaction product is then separated, for example by addition of water if the solvent used is miscible with watencor, preferably, by evaporation of the solvent after elimination of the acid catalyst.

An alternative to the process for obtaining the compounds of the present invention consists of reacting. alkylor aryl-mercapto-methylenamide of alpha-halo-acetic acid re rates Patent 3,013,940 Patented Dec. 19, 1961 2 with alkaline salts of 0,0-dialkyl-thioor dithiophos'- phoric acids. according to the-following scheme:

where R, R" and X havethe above-mentioned meaning; Hal is a halogen and Me is an alkali or alkaline earth metal or radical.

Said reaction is carried out in atotal or partial solu-. tion or suspension of both reactants, using assolvent, or as dispersing agent, a liquid preferably inert to one or both reactants, e.g. ketones, ester, alcohols; etc. or mixtures thereof, atroom temperature for a sufiicient time, or at the reflux temperatureof the solvent, until the metal halide is completely precipitated;

The reaction product is then separated by drowning it in water, or by solvent evaporation, under suction for example, after removal of the inorganic salt by filtration.

The following examples illustrate the present invention however without limiting itsscope.

EXAMPLE 1' 54 g. N-oxymethylamide of 0,0-diethyl-dithiophosphorylacetic acid (melting point 71 -72" 0.), of the formula oonn HO CHTF-NH-O 0crn,s-fi

are added to a solution of 14 g. methylmercaptan in 100 cc. ethyl acetate. 8' cc. benzene saturated with gaseous HCl are also added and the vessel is heated at 45" C1 for 6 hours while stirring and then left at' room tem-' perature for 15 hours;

The liquid obtained is washed with 30 cc. of a coldsaturate'd NaHCO solution. and" then with cc. water. it is dried on Na SO and evaporated under vacuum. The residual product; consisting of methyl-mercaptomethylenamide of 0,0 diethyl dithiophosphorylacetic acid, is a white crystalline solid weighing 51 g.. A sample, crystallized from an ethyl ether-petroleum ether mixture, has a melting'point 10f49-49.5 CL

EXAMPLE. 21

6 g; methyl mercapto-methylenamide of monochl'oro acetic acid (melting point -156 CL), of the formula and 10.0 g. potassium Q,0-diethylrdithiophosphate. are allowed to react in cc. acetone at room temperature for 15 hours,

The mixture is drowned in 200cc. water and the pro 'cipitate-is filtered and washed with water.

3 EXAMPLE 3 38.2 g. methyl-mereapto-methylenamide of monochloroacetic acid, 52.0 g. potassium 0,0-diethyl-thiophosphate and 150 cc. acetone are mixed and stirred at room temperature for 24 hours. The mixture is then refluxed for 1 hour. The potassium chloride thus formed is separated by filtration and the filtrate is heated under suction to eliminate the solvent.

The residual product (71 g.) consisting of methylmercapto-methylenamide of 0,0-diethyl-thio-phosphorylacetic acid is a clear oil, with a slight straw-yellow color and an index of refraction n =1.5079.

EXAMPLE 4 49 g. N-oxymethylarnide of 0,0-dimethyl-dithiophosphorylacetic acid (melting point 82-83 C.) are added to a solution of 12 g. methyl-mercaptan in 80 cc. benzene. 6 cc. benzene, previously cold saturated with gaseous HCl are added and the closed container is heated to 45-50 C. for 6 hours while frequently stirring, and is then left at room temperature for 15 hours. The benzene solution of the reaction product, which is turbid because of the presence of water, is washed with a diluted NaHCO solution until it is neutral, and then dried on Na SO and evaporated under vacuum.

The residue consists of 51.5 g. methyl-mercapto-methylenamide of 0,0-dimethyl-dithiophosphoryl-acetic acid, which can be purified by crystallization from an ethyl ether-petroleum ether mixture and has a melting point of EXAMPLE 5 54.5 g. N-oxymethylamide of 0,0-diethyl-dithiophosphorylacetic acid, 13.7 g. ethyl mercaptan and 100 cc. ethyl acetate are placed in a vessel. 8 cc. benzene saturated with HCl are added, and the mixture heated to 45 C. for 6 hours and left at room temperature for hours.

The desired product, that is, the ethyl-mercapto-meth ylenamide of 0,0-diethyl-dithiophosphorylacetic acid is obtained, after the usual treatment, in the form of a slightly opalescent oil, weighing 54.2 g. This product, after purification by crystallization from an ether-petroleum ether mixture, appears in the form of colorless crystals having a melting point of 28.5-29.5 C.

EXAMPLE 6 49 g. N-oxymethylamide of 0,0-dimethyl-dithiophosphorylacetic acid, 13.7 g. ethyl mercaptan and 100 cc. ethyl acetate, treated as described in the preceding example, yield 52.5 g. ethyl-mercapto-methylenamide of 0,0-dimethyl-dithiophosphorylacetic acid with a melting point of 4l42 C. (after crystallization from ethyl etherpetroleum ether).

EXAMPLE 7 54.5 g. N-oxymethylamide of 0,0-diethyl-dithiophosphorylacetic acid, 16.8 g. isopropyl mercaptan and 120 cc. ethyl acetate are heated to 48 C. for 6 hours in the presence of traces of anhydrous HCl. After 15 hours a washing with an aqueous alkaline solution is carried out, and the solvent is eliminated under suction. 60 g. isopropyl-mercapto-methylenamide of 0,0-diethyl-dithiophosphorylacetic acid are obtained, as a colorless solid. It is crystallized from 80% methyl alcohol and melts at 42-43 C.

EXAMPLE 8 18.1 g. isopropyl-mereapto'methylenamide of chloroacetic acid (M.P. 68-70 C.), 20.8 g. potassium 0,0-diethyl-thiophosphate and 80 cc. acetone are allowed to react at a temperature not thigher than C. for 24 hours. The reaction mixture is then kept for 1 hour at the refluxing temperature of the solvent. After filtration of the potassium chloride and elimination of the solvent, 32 g. isopropyl-mereapto-methylenamide of 0,0-diethylthiophosphorylacetic acid are obtained in the form of a clear oil, slightly yellow colored, having a refraction index of n =l.4978.

EXAMPLE 9 49 g. N-oxymethylenamide of 0,0-dimethyl-dithiophosphorylacetic acid, 16.8 g. isopropyl mercaptan and cc. ethyl acetate, added with 10 cc. benzene saturated with HCl, are stirred at 45 C. for 3 hours and then left at room temperature for 30 hours. The mixture is stirred first with 25 cc. of a diluted aqueous NaHCO solution, then with 50 cc. H O. After drying on MgSO it is evaporated under vacuum.

The residual product consists of isopropyl-mercaptomethyienamide of 0,0-dimethyl-dithiophosphorylacetic acid. It is a white, colorless solid, crystallizable from diluted methyl alcohol, having a melting point of 59.5- 60.5 C.

EXAMPLE 10 27.3 g. N-oxymethylamide of 0,0-diethyl-dithiophosphorylacetic acid are mixed with 11 g. thiophenol. 4 drops cone. hydrochloric acid are added and the mass is heated to 45 C. while stirring until it becomes homogeneous. It is then left to stand for 20 hours. The solid mass thus obtained is broken, washed with NaHCO solution and filtered. 31 g. phenyl-mercapto-methylenarnide of 0,0-diethyl-dithiophosphorylacetic acid, melting point 6061 C. (from methyl alcohol), are obtained.

The products comprised in the aforementioned general formula have shown interesting insecticidal properties which make them useful for practical application in antiparasitic control. This was substantiated as follows:

Methods for evaluating the biological activity of the pesticidal compounds of the present invention (1) Aphicidal activity.-Young broad bean plants, infested by aphids (Aphz's fabae Scop.) are dipped for a few seconds in suitably formulated aqueous dispersions of the product to be examined, and then kept and checked under determined conditions of lightning, temperature and moisture suitable for the insects. 24 hours after the treatment the insect mortality with the various doses of the product is observed under a binocular microscope.

(2) Acaricide activity.'Ihe test is carried out as in determining the aphicidal activity, using the red spider (Tetranychas telarias L.) grown on young bean plants.

(3) Ovicidal activity.Grown female red spiders (T. telarias L.) are placed for 24 hours on young bean plants, having only cotyledon leaves, for the egg deposition. The grown insects are then eliminated with a jet of compressed air and the plants are treated as in method 1. The egg mortality is controlled after 6 days under the binocular microscope.

(4) Systemic activity by root abs0rpti0n.--The hypogeous portion of young broad bean plants infested by aphids (Aphis fabae Scop.) is introduced into small colored glass vases containing aqueous dispersions of the test products. The small vases are kept in a room suitable for the insects for 8 days, while observing daily the mortality of the aphids living on the hypogeous portion of the plants.

(5) Insecticidal activity on flies by topical application-By means of a microsyringe Agla one drop (1 mm?) of acetone solution of the test product is applied to the dorsal region of 4 days aged female domestic flies (Mascal domestica L.) (a strain grown in the laboratory, sensitive to the organic chlorinated products and to other insecticides). The insects are kept under observation in suitable small metallic cages and the mortality control is carried out after 24 hours.

(6) Insecticidal activity -on flies by tharsal absorption-Female domestic flies (Masca domestica L.) like those used in the preceding method, are introduced into 1000 cc. glass beakers whose inner sulface has been ILL coated with a uniform film of the product to be examined. These beakers, closed with a gauze, are kept in a room under suitable temperature and moisture conditions, the knockdown of the insects in the first 2 hours andthe mortality after 20 hours being determined.

TABLE I. RESULTS OF THE EVALUATION OF THE BIOLOGICAL ACTIVITY Active Ovicidal S stem'ic sub- Aphids, Acari, y stance mormorconc., tality tality a.s. cone. morp.p.m. morpement taiitytalit'y 0.2 100 100 0.2 100 l 250 100 Ex. 1 Methylmercaptoniethylenamide of 0,0-dicthy1- dithiophosphorylacetic acid. 8:83 6 32 g 5 n 0.2 100 100 Z2 s2 250T 100 Ex. 3-Methylmcrcaptomethylenamide of 0,0-d1ethyl- V thiophosphorylacetic acid. 8:83 g 5 v 0.2 100 100 0:2 65 250 100 Ex. 4 Mcthylmercaptomethylenamide of O O-dimethyldithiophosphorylacetic acid. 83 8 5 8 g 5 0.2 100. 100 012 100 2:0 100 Ex. 5 Ethylniercaptomethylenamide of 0,O -d1ethyldithiophosphorylacetic acid. 8'86 8g 6 g 5 g i 0.2 100 100 0.2 82 250' 100 Ex. 6Ethylmei captomethylenamide of 0,0-dimethy1- I dithiophosphorylacetic acid. 8:86 8g 8 g 5 g 1 0.2. 100 100 012 100 250' 92 En. 7-150propylmercaptornethylenamide of 0,0-di- 0 O4 100 1 V 00 0.1 100 25 ethylthiophosphorylacetlc acid. 3 2 100 2 5 0 Ex. 8Isopr0pylinercaptomethylenamide of 0 O-di- 1 230. 100 ethylthiophosphorylacetic acid. 83 8g g 5 8 0. 2 100 100 0. 2 92 250' 100 Ex. 9-Is0propylrnercaptomethylenamide of 0,0-di- 0 O4 99 100 0.1. 75. 100 methyldithiophcsphorylacetic acid. 0.008 29 (L05 58 2 5 10 TABLE II Topical appL, 7 Beaker, g./m.

per fly Ex. 1Methylrncrcaptomethylenamide of 0,0-diethyldithiophosphorylacetic acid percent mortality 100 99 5 100 94 4 Ex. 4-Methy1mercapto1nethy 0,0- dimethyldithiophosphorylacetic acid percent mort 100 100 16 100 79 5 Ex.3-Methylrnercaptomethylenamideo iethylthiophosphorylacctic acid, percent mortality 100 77 3 100 83 Ex. 5-Ethylmercaptomethylenamide of 0,0-diethyidithiophosphorylacetic acid, percent mortality 100 96 1 100 1 Ex. 6-Ethylmercaptoinethylenaimde of 0,0 1 1 methyldithiophosphorylaeetic acid, percent mortality 100 92 0 100 67 1 Ex. 7Is0propylmercaptomethylenamide of 0,0-

diethyldithiophosphcrylacetic acid, percent mortality 100 72 0 100 1 Ex. 8-Isopropylmercaptomethylenamide of 0,0- 3

diethylthiophosphorylacetic acid, percent mortality 99 11 0 100 73 17 Ex. 9Iscpropyhnercaptomethylenamide of 0,0-

dimethyldithiophospliorylacetic acid, percent mortality 100 76 1 100 61 4 Determination of the acute toxicity by oral or intmve- TABLE III.

nous application (on warm-blooded animals) of mercapto-methylenamides 0f 0,0-dialkyl-thi0- and dithio- 60 Toxicity e. phosphorylacetic acids V endoyenpns qral. A determination has been made of the acute toxicity, iapphcamn apphcatmn per oral or intravenous administration, of the compounds Parathion of the present patent application on warm-blooded ani- Ex. 1 Mthyifiiffiiifiiifiigfig fifi5Y6 mals. The determination of the acute toxicity per os 9 l i l 7 Ea.3-Methylmercaptomethylenamide ofacid wa carried out by gastric sounding and the administra- DOggiettfiylphcsphorylacetic acid 9.6 11.5 1 x. c ymercaptometiylenamide of 0,- H011 of a dimeihyl-acetamidc solution of the. test. prod- Ominethyldithiophosphorylacefic Mum 155 550 nets on small white rats weighing 18-20 g. The intera ??ligllwrcalptflrgllet y namide of 0,-

r ference of the solyent n the tOXlC manifestations can be Ex. (IT- n51 in ig ii i iiig i ii e bi'611' cgns dered as h ib1 O-dimethyldithiophosphorylacetic acid 130 225 7 n Ex. 7I sopr0p y1mer x ptomcthylenamide of The; determination of me acute toxicity by mtrave- 0,0-diethyldithiophospharylaceticacids,--- as 7 e4 "nous application was carried out with the said products dissolved in demethylacetamide, on small white rats weighing 1820 g.

In Table I, the abbreviation as. means active substance.

In Table II, the symbol 'y means a millionth of a gram, and Beaker g./m. means, in reference to the antecedent paragraph designated (6), that the tests are carried out by introducing the flies into a beaker (cylindrical glass surface) whose inner walls have been sprayed with a solution of the active substance, to obtain a film containing a given number of grams per square meter of said surface.

The term LD 50? means lethal dose by which a 50% mortality is obtained.

We claim:

1. A process of preparing a mercapto-methylenamide of an 0,0-dialkyl-thio-phosphorylacetic acid, characterized in that a mercaptan is reacted with an N-methylolamide of an 0,0-dialkyl-thio-phosphorylacetic acid, the reactants and the reaction being according to the following reaction scheme:

where X is taken from the group consisting of oxygen and sulfur, R is taken from the group consisting of lower alkyl and phenyl radicals, and R is a lower alkyl radical, the reaction being carried out in a liquid organic diluent that is inert in the reaction, and at a temperature between about 20 C. and 100 C.

2. A process of preparing a mercapto-methylenamide of an 0,0-dialkyl-thio-phosphorylacetic acid, characterized in that a mercaptan is reacted with an N-rnethylolamide of an 0,0-dialkyl-thio-phosphorylacetic acid, the reactants and the reaction being according to the following reaction scheme:

where X is taken from the group consisting of oxygen and sulfur, R is taken from the group consisting of lower alkyl and phenyl radicals, and R is a lower alkyl raical, the reaction being carried out in an inert organic diluent in the presence of an acid.

3. The process of claim 2, carried out at a temperature between and 150 C.

4. A process for preparing a mercapto-methylenamide of an 0,0-dialkyl-thio-phosphorylacetic acid, characterized in that a mercaptomethylen-alpha-halo-acetamide is reacted with a salt of an 0,0-dialkyl-thio-phosphoric acid, the reactants and the reaction being according to the following reaction scheme:

where X is taken from the group consisting of oxy en and sulfur, R is taken from the group consisting of lower alkyl and phenyl radicals, and R is a lower alkyl radical, the reaction being carried out in an organic solvent for at least one of the reactants, and at a temperature between 0 and 150 C.

5. The process of clahn 4, carried out in an organic solvent for at least one of the reactants, at a temperature between not higher than about 50 C.

6. As an antiparasiticide, a compound taken from the group consisting of of 0,0-diethyl-dithioof 0,0-diethyl-di- 7. As an antiparasiticide, methylmercapto-methylenamide of 0,0-dimethyl-dithiophosphorylacetic acid.

8. As an antiparasiticide, methylmercapto-methylenamide of 0,0-diethyl-dithiophosphorylacetic acid.

9. As an antiparasiticide, methylmercapto-methylenamide of 0,0-diethyl-thiophosphorylacetic acid.

10. As an antiparasiticide, ethylmercapto-methylenamide of 0,0-dimethyl-dithiophosphorylacetic acid.

11. As an antiparasiticide, ethylmercapto-methylenamide of 0,0-diethyl-dithiophosphorylacetic acid.

12. As a pest control agent, a compound of the formula where X is taken from the group consisting of oxygen and sulfur, R is taken from the group consisting of lower alkyl and phenyl radicals, and R is a lower alkyl radical.

13. A process of preparing a mercapto-methylenamide of an 0,0-dialkyl-thio-phosphorylacetic acid, characterized in that a mercaptan is reacted with an N-methylolamide of an 0,0-dialkyl-thio-phosphorylacetic acid, the reactants and the reaction being according to the following reaction scheme:

where X is taken from the group consisting of oxygen and sulfur, R is taken from the group consisting of lower alkyl and phenyl, and R is a lower alkyl radical, the reaction being carried out in a liquid organic diluent, and at a temperature between about 20 C. and C., said diluent being taken from the group consisting of ethyl acetate, acetone, and benzene.

14. In the art of controlling insect pests, the improve- 9 ment comprising applying to the locality of the pest, in a concentration toxic to the pest, a compound of the formula:

where X is taken from the group consisting of oxygen and sulfur, R is taken from the group consisting of lower alkyl and phenyl radicals, and R is a lower alkyl radical.

15. In the art of controlling insect pests, the improvement comprising applying to the locality of the pest, in a concentration toxic to the pest, a compound taken from the group consisting of Methylrnercapto-methylenamide of 0,0-dimethyl-dithiophosphorylacetic acid Methylmercapto-methylenan'iide of 0,0'-diethy1-dithio'- phosphorylacetic acid Methylmercapto-methylenamide of 0,0-diethy1-thiophosphorylacetic acid Ethylmercapto-methylenamide of O,O-dimethyl-ditl1iophosphorylacetic acid Ethylmercapto-methylenamide phosphorylacetic acid Isopropylmercapto-methylenamide of 0,0 dimethyl-dithiophosphorylacetic acid of 0,0-diethyl-dithio- Isopropylmercapto-methylenamide thiophosphorylacetic' acid Isopropylmercapto-methylenamide of 0,0'-diethyl-thiophosphorylacetic acid, and

of 0,0-diethy1-di- Phenylmercapto-methylenamide of 0,0-diethyl-dithiophosphorylacetic acid 16. The process defined in claim 15, the insect pest being taken from the class consisting of aphids, acari, flies, and their ova.

References Cited in the file of this patent UNITED STATES PATENTS OTHER REFERENCES Schoberl et al.: Methoden der Organischen Chemie,

Band IX, p. 117 (1955).

De Pietri-Tonelli: Chem, Ahst., vol. 50, No. 21, C01. 16, 021 (1956). 

12. AS A PEST CONTROL AGENT, A COMPOUND OF THE FORMULA 